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Tumor-specific immunity induced by cryoablation in a murine renal cell carcinoma model.

Kim HK, Pyun JH, Cho S, Kang SG, Lee JG, Kim JJ, Cheon J, Park HS, Kang SH - Korean J Urol (2014)

Bottom Line: The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area.The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Korea University Anam Hospital, Seoul, Korea.

ABSTRACT

Purpose: To evaluate tumor-specific immunity and define the mechanisms involved in the cryoimmunologic response, we compared the tumor control efficacy and immunologic responses of cryoablation with those of surgical excision in a tumor rechallenge model.

Materials and methods: Sixty BALB/c mice with RENCA tumors that were generated in the left flank area underwent cryoablation or radical excision. The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area. The recurrence rate after tumor rechallenge in each group was then observed. To assess the immunologic response of each treatment modality, fluorescent-activated cell sorting (FACS) analysis and a cytotoxicity assay using (51)Cr release were performed.

Results: After reinoculation of the RENCA cells, the rate of tumor growth was significantly higher in the surgical excision group than in the cryoablation group (94.4% vs. 11.1%, p=0.001). In the cryoablation group, the tumor growth rate was significantly increased after rechallenge of CT26 cells compared with RENCA (94.1% vs. 11.1%, p=0.001). The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.

Conclusions: These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

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Result of the fluorescent-activated cell sorting (FACS) analysis of the cryoablation and surgical excision. (A) The CD3, CD4, CD8, and natural killer cell counts measured by the FACS assay were significantly increased in the cryoablation group compared to the surgical excision group. The CD19 cell count was higher in the surgical excision group, but this difference was not statistically significant. *p<0.05, by Mann-Whitney U test. (B) The cytotoxic activity of lymphocyte after cryoablation. Mice with RECNA tumors treated by either cryoablation or surgical excision were sacrificed and spleens were harvested for a cytotoxicity assay against RENCA cell line. The significantly increased cytotoxicity of cryoablation group, compared with surgical excision or tumor control group, was manifested at E:T ratio of 40:1, and maintained to 5:1. The cytotoxicity of surgical excision was statistically increased also compared to control group, from E:T ratio of 40:1 to 10:1 (*p<0.05, by Kruskal-Wallis test and Mann-Whitney U test compared cryoablation group to surgical excision group or control group. †p<0.05, by Mann-Whitney U test compared excision group to control group). E:T ratio, ratios of effecter to target cells.
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Figure 2: Result of the fluorescent-activated cell sorting (FACS) analysis of the cryoablation and surgical excision. (A) The CD3, CD4, CD8, and natural killer cell counts measured by the FACS assay were significantly increased in the cryoablation group compared to the surgical excision group. The CD19 cell count was higher in the surgical excision group, but this difference was not statistically significant. *p<0.05, by Mann-Whitney U test. (B) The cytotoxic activity of lymphocyte after cryoablation. Mice with RECNA tumors treated by either cryoablation or surgical excision were sacrificed and spleens were harvested for a cytotoxicity assay against RENCA cell line. The significantly increased cytotoxicity of cryoablation group, compared with surgical excision or tumor control group, was manifested at E:T ratio of 40:1, and maintained to 5:1. The cytotoxicity of surgical excision was statistically increased also compared to control group, from E:T ratio of 40:1 to 10:1 (*p<0.05, by Kruskal-Wallis test and Mann-Whitney U test compared cryoablation group to surgical excision group or control group. †p<0.05, by Mann-Whitney U test compared excision group to control group). E:T ratio, ratios of effecter to target cells.

Mentions: For the statistical analysis, the local tumor growth rate after tumor rechallenge was analyzed by using chi-square tests (Table 1). The results of the FACS analysis were analyzed by using the Mann-Whitney U test (Fig. 2A). The cytotoxic activity of lymphocytes among the cryoablation, surgical excision, and tumor control groups was compared by using the Kruskal-Wallis and Mann-Whitney U tests (Fig. 2B). All statistical analyses were processed by using SPSS ver. 17.0 (SPSS Inc., Chicago, IL, USA) and p-values below 0.05 were considered significant.


Tumor-specific immunity induced by cryoablation in a murine renal cell carcinoma model.

Kim HK, Pyun JH, Cho S, Kang SG, Lee JG, Kim JJ, Cheon J, Park HS, Kang SH - Korean J Urol (2014)

Result of the fluorescent-activated cell sorting (FACS) analysis of the cryoablation and surgical excision. (A) The CD3, CD4, CD8, and natural killer cell counts measured by the FACS assay were significantly increased in the cryoablation group compared to the surgical excision group. The CD19 cell count was higher in the surgical excision group, but this difference was not statistically significant. *p<0.05, by Mann-Whitney U test. (B) The cytotoxic activity of lymphocyte after cryoablation. Mice with RECNA tumors treated by either cryoablation or surgical excision were sacrificed and spleens were harvested for a cytotoxicity assay against RENCA cell line. The significantly increased cytotoxicity of cryoablation group, compared with surgical excision or tumor control group, was manifested at E:T ratio of 40:1, and maintained to 5:1. The cytotoxicity of surgical excision was statistically increased also compared to control group, from E:T ratio of 40:1 to 10:1 (*p<0.05, by Kruskal-Wallis test and Mann-Whitney U test compared cryoablation group to surgical excision group or control group. †p<0.05, by Mann-Whitney U test compared excision group to control group). E:T ratio, ratios of effecter to target cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265719&req=5

Figure 2: Result of the fluorescent-activated cell sorting (FACS) analysis of the cryoablation and surgical excision. (A) The CD3, CD4, CD8, and natural killer cell counts measured by the FACS assay were significantly increased in the cryoablation group compared to the surgical excision group. The CD19 cell count was higher in the surgical excision group, but this difference was not statistically significant. *p<0.05, by Mann-Whitney U test. (B) The cytotoxic activity of lymphocyte after cryoablation. Mice with RECNA tumors treated by either cryoablation or surgical excision were sacrificed and spleens were harvested for a cytotoxicity assay against RENCA cell line. The significantly increased cytotoxicity of cryoablation group, compared with surgical excision or tumor control group, was manifested at E:T ratio of 40:1, and maintained to 5:1. The cytotoxicity of surgical excision was statistically increased also compared to control group, from E:T ratio of 40:1 to 10:1 (*p<0.05, by Kruskal-Wallis test and Mann-Whitney U test compared cryoablation group to surgical excision group or control group. †p<0.05, by Mann-Whitney U test compared excision group to control group). E:T ratio, ratios of effecter to target cells.
Mentions: For the statistical analysis, the local tumor growth rate after tumor rechallenge was analyzed by using chi-square tests (Table 1). The results of the FACS analysis were analyzed by using the Mann-Whitney U test (Fig. 2A). The cytotoxic activity of lymphocytes among the cryoablation, surgical excision, and tumor control groups was compared by using the Kruskal-Wallis and Mann-Whitney U tests (Fig. 2B). All statistical analyses were processed by using SPSS ver. 17.0 (SPSS Inc., Chicago, IL, USA) and p-values below 0.05 were considered significant.

Bottom Line: The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area.The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Korea University Anam Hospital, Seoul, Korea.

ABSTRACT

Purpose: To evaluate tumor-specific immunity and define the mechanisms involved in the cryoimmunologic response, we compared the tumor control efficacy and immunologic responses of cryoablation with those of surgical excision in a tumor rechallenge model.

Materials and methods: Sixty BALB/c mice with RENCA tumors that were generated in the left flank area underwent cryoablation or radical excision. The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area. The recurrence rate after tumor rechallenge in each group was then observed. To assess the immunologic response of each treatment modality, fluorescent-activated cell sorting (FACS) analysis and a cytotoxicity assay using (51)Cr release were performed.

Results: After reinoculation of the RENCA cells, the rate of tumor growth was significantly higher in the surgical excision group than in the cryoablation group (94.4% vs. 11.1%, p=0.001). In the cryoablation group, the tumor growth rate was significantly increased after rechallenge of CT26 cells compared with RENCA (94.1% vs. 11.1%, p=0.001). The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.

Conclusions: These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

Show MeSH
Related in: MedlinePlus